The proposed study will determine whether immunization (ocular or intraperitoneal) with an avirulent, HSV-1 thymidine kinase negative (TK-) mutant will protect the mouse against (1) keratitis, (2) death and (3) the establishment of latency after ocular challenge with three virulent wild-type HSV-1 TK+ strains. Outbred ICR mice (4-6 weeks old) will be divided into two treatment groups and immunized in a masked fashion by corneal scarification or intraperitoneal injection with HSV-1 TK- (0% TK activity or media control. Two weeks later, all mice will be challenged ocularly with three coded virulent, wild-type HSV-1 TK+ strains (NIH 11124, Shealy, R.E.). The animals will be evaluated for keratitis two days post-challenge and followed daily for survival for 28 days. At that time, the trigeminal ganglia will be explanted, minced and cocultivated on Vero cells. Recovered latent HSV-1 virus as determined by progressive cpe on Vero cells will be harvested and the thymidine kinase phenotype (TK+ or TK-) will be determined by BUDR-methylcellulose titrations. The results will indicate whether further work should be pursued with HSV-1 TK- mutants as a potential herpes vaccine.